What is the role of specific neuronal cell types for sensation and cognition
I. Purpose of the experiments: How do cortical circuits process sensory stimuli that leads to perception and cognition? Sensory input is encoded by complex interactions between excitatory neurons and a diverse population of inhibitory cells. However, the individual role of these cell types remains poorly understood. This is mainly due to the technical challenges of recording the activity of identified cell types in-vivo, in response to sensory stimuli. Therefore, we use the following combined approach: 1) Electrophysiology and two-photon imaging to record the activity of thousands of identified neurons in-vivo. 2) Head-fixed decision and foraging tasks for mice.
II. Expected distress for the animals. To be able to use electrophysiology and microscopy to measure neural activity, a small titanium implant is fixed on the skull so mice can be trained to perform various cognitive tasks while the head is immobile. Mice are then trained in foraging tasks or sensory discriminations tasks in return for rewards. The health and comfort of our mice is essential, as this is elementary for learning the tasks. The discomfort of the titanium implant surgery is alleviated using standard analgesia and is short lasting (approx. 2 days). For behavioural training, to avoid stress during the first 2-3 days, mice are acclimatised to the training apparatus. After the first 2-3 days we experience that mice actually likely doing the behavioural task because they receive rewards, and because the task may be more exciting than their cage life.
III. Expected scientific or societal benefit: Neural diseases are an enormous burden from a societal and economic perspective. Few of these have good treatment, and we believe this is due to a lack of understanding of how a healthy brain works. Thus, this work will not only reveal the roles of specific cell types in the brain during behaviour in the healthy brain, but will also help us understand what goes wrong during neurodegenerative or neuropsychiatric diseases.
IV. The number of animals and species: Seven researchers will use 30 mice per year each, over 4 years (total 840 mice). This includes animals for pilot experiments and for data analysis. This number is based on our previous experience and considering the statistical tests that are needed. Some of these mice are transgenic, Cre-recombinase and GFP-expressing mouse lines that have no phenotype or cause any known discomfort.
V. how demands for replacement, reduction and improvement will be adhered to. REPLACEMENT: The mouse brain architecture has many similarities to the human brain on the circuit level. For decades, monkeys were the gold standard for studying brain physiology but my lab and others have found that also mice can be trained to perform complex cognitive tasks, hence reducing the need for monkey and primate research. REDUCTION: We will keep the number of mice to a minimum. The experience that we have will help to optimally organize the breeding colonies, and to teach the students to perform high quality surgeries so data can be obtained with fewer mice. REFINEMENT: The mouse cages are enriched with running wheels and shelters. During behavior experiments, mice are trained with one person with whom they get comfortable.
II. Expected distress for the animals. To be able to use electrophysiology and microscopy to measure neural activity, a small titanium implant is fixed on the skull so mice can be trained to perform various cognitive tasks while the head is immobile. Mice are then trained in foraging tasks or sensory discriminations tasks in return for rewards. The health and comfort of our mice is essential, as this is elementary for learning the tasks. The discomfort of the titanium implant surgery is alleviated using standard analgesia and is short lasting (approx. 2 days). For behavioural training, to avoid stress during the first 2-3 days, mice are acclimatised to the training apparatus. After the first 2-3 days we experience that mice actually likely doing the behavioural task because they receive rewards, and because the task may be more exciting than their cage life.
III. Expected scientific or societal benefit: Neural diseases are an enormous burden from a societal and economic perspective. Few of these have good treatment, and we believe this is due to a lack of understanding of how a healthy brain works. Thus, this work will not only reveal the roles of specific cell types in the brain during behaviour in the healthy brain, but will also help us understand what goes wrong during neurodegenerative or neuropsychiatric diseases.
IV. The number of animals and species: Seven researchers will use 30 mice per year each, over 4 years (total 840 mice). This includes animals for pilot experiments and for data analysis. This number is based on our previous experience and considering the statistical tests that are needed. Some of these mice are transgenic, Cre-recombinase and GFP-expressing mouse lines that have no phenotype or cause any known discomfort.
V. how demands for replacement, reduction and improvement will be adhered to. REPLACEMENT: The mouse brain architecture has many similarities to the human brain on the circuit level. For decades, monkeys were the gold standard for studying brain physiology but my lab and others have found that also mice can be trained to perform complex cognitive tasks, hence reducing the need for monkey and primate research. REDUCTION: We will keep the number of mice to a minimum. The experience that we have will help to optimally organize the breeding colonies, and to teach the students to perform high quality surgeries so data can be obtained with fewer mice. REFINEMENT: The mouse cages are enriched with running wheels and shelters. During behavior experiments, mice are trained with one person with whom they get comfortable.